METHOTREXATE SHOULD BE USED ONLY BY PHYSICIANS WHOSE
KNOWLEDGE AND EXPERIENCE INCLUDE THE USE OF
ANTIMETABOLITE THERAPY BECAUSE OF THE POSSIBILITY OF
SERIOUS TOXIC REACTIONS (WHICH CAN BE FATAL):
DEATHS HAVE BEEN REPORTED WITH THE USE OF METHOTREXATE IN THE TREATMENT OF MALIGNANCY, PSORIASIS, AND RHEUMATOID ARTHRITIS.
A premethotrexate evaluation is critical before prescribing. The evaluation should include a thorough history, current medications, renal and hepatic evaluation.
PATIENTS SHOULD BE CLOSELY MONITORED FOR BONE MARROW, LIVER, LUNG AND KIDNEY TOXICITIES.
Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high dosage) along with some non-steroidal anti-inflammatory drugs (NSAIDs).
Major toxic effects, such as hepatic, pulmonary, renal and bone marrow abnormalities, require careful monitoring.
contraindications include renal dysfunction, liver disease, active infectious disease and excessive alcohol consumption.
Both women and men of reproductive age should use birth control during methotrexate therapy.
Methotrexate can be given orally, intramuscularly or by subcutaneous injection
The mechanism of action in rheumatoid arthritis is unknown; it may affect immune function. Two reports describe in vitro methotrexate inhibition of DNA precursor uptake by stimulated mononuclear cells, and another describes in animal polyarthritis partial correction by methotrexate of spleen cell hyporesponsiveness and suppressed IL 2 production. Other laboratories, however, have been unable to demonstrate similar effects. Clarification of methotrexate’s effect on immune activity and its relation to rheumatoid immunopathogenesis await further studies.
Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one carbon groups in the synthesis of purine nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of methotrexate. When cellular proliferation in malignant tissues is greater than in most normal tissues, methotrexate may impair malignant growth without irreversible damage to normal tissues.
Rheumatoid Arthritis including Polyarticular-Course Juvenile Rheumatoid Arthritis Methotrexate is indicated in the management of selected adults with severe, active, rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis, who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose nonsteroidal anti-inflammatory agents (NSAIDs). Aspirin, NSAIDs, and/or low dose steroids may be continued, although the possibility of increased toxicity with concomitant use of NSAIDs including salicylates has not been fully explored.
Steroids may be reduced gradually in patients who respond to methotrexate.
(package insert)
DEATHS HAVE BEEN REPORTED WITH THE USE OF METHOTREXATE IN THE TREATMENT OF MALIGNANCY, PSORIASIS, AND RHEUMATOID ARTHRITIS.
A premethotrexate evaluation is critical before prescribing. The evaluation should include a thorough history, current medications, renal and hepatic evaluation.
PATIENTS SHOULD BE CLOSELY MONITORED FOR BONE MARROW, LIVER, LUNG AND KIDNEY TOXICITIES.
Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high dosage) along with some non-steroidal anti-inflammatory drugs (NSAIDs).
Major toxic effects, such as hepatic, pulmonary, renal and bone marrow abnormalities, require careful monitoring.
contraindications include renal dysfunction, liver disease, active infectious disease and excessive alcohol consumption.
Both women and men of reproductive age should use birth control during methotrexate therapy.
Methotrexate can be given orally, intramuscularly or by subcutaneous injection
The mechanism of action in rheumatoid arthritis is unknown; it may affect immune function. Two reports describe in vitro methotrexate inhibition of DNA precursor uptake by stimulated mononuclear cells, and another describes in animal polyarthritis partial correction by methotrexate of spleen cell hyporesponsiveness and suppressed IL 2 production. Other laboratories, however, have been unable to demonstrate similar effects. Clarification of methotrexate’s effect on immune activity and its relation to rheumatoid immunopathogenesis await further studies.
Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one carbon groups in the synthesis of purine nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of methotrexate. When cellular proliferation in malignant tissues is greater than in most normal tissues, methotrexate may impair malignant growth without irreversible damage to normal tissues.
Rheumatoid Arthritis including Polyarticular-Course Juvenile Rheumatoid Arthritis Methotrexate is indicated in the management of selected adults with severe, active, rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis, who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose nonsteroidal anti-inflammatory agents (NSAIDs). Aspirin, NSAIDs, and/or low dose steroids may be continued, although the possibility of increased toxicity with concomitant use of NSAIDs including salicylates has not been fully explored.
Steroids may be reduced gradually in patients who respond to methotrexate.
(package insert)
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